Venous disease is common, a major cause of morbidity and occasionally mortality, and accounts for 30% of all cardiovascular disease expenditures. Venous disease definitions have often confused symptoms and signs with pathophysiologic abnormalities. In our previous venous prevalence study, using hierarchical categories, we accurately established in a multi-ethnic population the presence or absence, and degree of concordance, of visible disease -normal (NL), varicose veins (W), trophic changes (TCS), and functional disease (reflux or obstruction) by Duplex ultrasound -normal, superficial functional disease (SFD), deep functional disease (DFD). We documented the importance of leg-specific assessment, and reported prevalence by age, sex, and ethnicity, and the association of venous disease with risk factors, symptoms, and quality of life. To date, there has been no rigorous assessment of the incidence of venous disease in a defined population. The specific aims are: First, to determine the ten-year incidence of new venous disease, and progression of existing venous disease, in 1200 men and women (2400 legs) from our study population with known venous disease status at baseline. Incident disease will be defined as transition from visibly and functionally normal to W, TCS, SFD, or DFD. Progressive disease will be defined as a transition from W to TCS or from SFD to DFD, or progression within these categories. We will separately determine the incidence of venous thrombosis and pulmonary embolism. Second, to evaluate risk factors for incident/progressive venous disease, focusing on risk factors potentially biased by "reverse causality" in prevalence studies; i.e., venous disease may cause rather than, or as well as, result from the risk factor; e.g., physical activity, obesity, and medication use, and selected stored plasma markers with a focus on thrombotic and inflammatory factors. Such data could impact prevention strategies. Third, to determine the temporal relation of symptoms with venous disease; i.e., can symptoms precede (as well as follow) incident/progressive disease? Such data could be important in clinical diagnosis of venous disease. Fourth, to evaluate change in the SF-36, a quality of life index, with incident/progressive venous disease, controlled for non-venous morbidity, to provide quantitative estimates of the burden of incident and progressive venous disease. This application builds on the seminal findings in our prevalence study, and since no such incidence data exist, is original and innovative. [unreadable] [unreadable] [unreadable]